Method of immunopotentiating and protecting an animal from E. coli infections using a combination of Rosa roxburghii, Artemisiae argyi folium and Brassica oleracea var. capitata L.

ABSTRACT

A method for immunopotentiating and protecting an animal from an infection caused by E. coli is described. The method comprises administering a composition containing Rosa roxburghii, Artemisiae argyi folium, and Brassica oleracea var. capitata L. to the animal.

This is a division of Ser. No. 08/285,980, filed Aug. 4, 1994, which isa division of Ser. No. 08/133,708, filed Oct. 7, 1993, now abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a medicinal agent or food whichpotentiates the immune system of an animal, including a human being, tothereby protect the animal from infection, and a feed or feedstuffhaving an immunopotentiating activity.

The present invention also relates to a medicinal agent or food forregulating a function of the digestive tract or gastrointestine of ananimal, including a human being, and a feed or feedstuff having theactivity of regulating the function of the digestive tract orgastrointestine of an animal.

Further, the present invention relates to a medicinal agent forimproving antibiotic absorption by an animal, including a human being,and a feed or feedstuff for improving antibiotic absorption by ananimal.

Furthermore, the present invention relates to a medicinal agent foraccelerating an animal growth or for improving an egg production rate,egg weight, egg quality or eggshell strength of an animal and a feed orfeedstuff having the activity of accelerating an animal growth or theactivity of improving an egg production rate, egg weight, egg quality oreggshell strength of an animal.

2. Description of the Related Art

With the recent progress in immunology, it has come to be thought thatthe various maladies and infectious diseases of an animal, including ahuman being, are caused by a weakening or deficiency in the immunesystem of the animal.

For example, a human being frequently suffers from a weakening ordeficiency in his immune system because of bronchial asthma, allergicdiseases, articular rheumatism, autoimmune diseases, nutritionaldisorders, surgical operation, aging, cancer, organ transplantation,pregnancy or the like, resulting in the complication of an infectiousdisease such as respiratory infections, sepsis or urinary infections.

Up to this time, various antibiotics have been administered to patientswith such maladies or infectious diseases. Meanwhile, large-scale orovercrowded raising has been employed in the fields of animal husbandryand aquaculture in order to raise livestock, poultries or fishefficiently, and in such raising, it has been also a practice toadminister a high dose of an antibiotic.

The repeated administration of an antibiotic for a long period causesthe generation of antibiotic-resistant bacteria to lower the effect ofthe antibiotic. Further, hospital infection has also become asignificant problem. Under these circumstances, it has been expected todevelop a preventive and therapeutic agent which can potentiate theimmune system while reducing the dosage of an antibiotic.

Further, the overcrowded raising employed in the fields of animalhusbandry and aquaculture has a problem in that various infectiousdiseases frequently break out because of stress or juvenileimmuno-deficiency. Furthermore, when a high dose of an antibiotic isadministered as a countermeasure against the problem, there occur otherproblems that the antibiotic is not completely consumed and thatantibiotic-resistant bacteria propagate in the environment.

Recently, animals, including human beings, have frequently suffered fromvarious gastrointestinal diseases which are caused by a lowering ordeficiency in the immune system, stress, dyspepsia or the like, and mostof which are accompanied with diarrhea.

For example, a human being becomes susceptible to an infectious diseaseof the digestive tract as his resistance lowers, and representativeexamples of the infectious disease include bacterial, vital andparasitic diarrheas. Further, the above gastro-intestinal diseases alsoinclude acute diarrheas caused by food poisoning and food allergy andchronic diarrheas caused by a disorder of digestion and absorption,excess gut hormone and colic diseases.

It has been the practice to administer an intestinal depressomotor forthe intestines, an astringent, an irritant-absorbing agent, a torpentfor enteric mucous membranes or various antibiotics against thesegastrointestinal diseases.

Meanwhile, large-scale or overcrowded raising has been employed in thefields of animal husbandry and aquaculture to raise livestock, poultriesor fish efficiently. In such raising, it has been a practice toadminister the above therapeutic agents for the treatment of diarrheacaused by stress or dyspepsia. Particularly, a large amount of anantibiotic has been used for the prevention of infectious diseases.

The administration of the above depressomotor or astringent isessentially a nosotropic means, while that of an antibiotic is anetiotropic one. However, the repeated administration of an antibioticfor the prevention of infectious diseases has a problem that thepreventive effect lowers owing to the generation of antibiotic-resistantbacteria.

Under these circumstances, it has been expected to develop a novelpreventive and therapeutic agent which can regulate gastrointestinalfunctions themselves and is safe.

Up to this time, various antibiotics have been administered to patientswith various maladies or infectious diseases. Meanwhile, large-scale orovercrowded raising has been employed in the fields of animal husbandryand aquaculture to raise livestock, poultries or fish efficiently. Insuch raising, it has been a practice to administer a high dose of anantibiotic.

With respect to the use of an antibiotic, however, there have beenpointed out problems such that the antibiotic accumulates in the body ofan animal to affect the body and that the administration of a morepotent antibiotic becomes necessary because of the generation ofantibiotic-resistant bacteria. Further, the administration of anantibiotic to an animal is problematic also in that the environment ispolluted with the antibiotic contained in the excrement of the animal.Under these circumstances, it has been expected that the dose of theantibiotic to be administered is reduced. In order to reduce the dose ofthe antibiotic, it has been believed effective that the absorption ofthe antibiotic through the digestive tract should be enhanced to attainan effect equal or superior to that attained by the administrationthereof in a high dose, even when the antibiotic is administered in alow dose. However, no substance which can improve the absorption of anantibiotic has been found as yet.

In preparing animal feed, various attempts have been widely made atimproving the feeding efficiency for animals and also at acceleratingthe growth thereof by adding various antibiotics to the feed,incorporating an increased amount of proteins into the feed, changingthe feeding method or improving the dosage form of the feed.

With respect to the use of an antibiotic, however, there have beenpointed out problems such that the antibiotic remains or accumulates inthe body of an animal to affect the body and that the administration ofa more potent antibiotic becomes necessary because of the generation ofresistant bacteria. Further, the administration of an antibiotic to ananimal is problematic also in that the environment is polluted with theantibiotic contained in the excrement of the animal. In addition, theeffects obtained by varying the feeding method and the dosage form ofthe feed are limited. Under these circumstances, it is necessary todevelop a safe and less problematic animal growth accelerator, feed andimprover for the egg production ratio, egg weight, egg quality oreggshell strength of animals.

DISCLOSURE OF THE INVENTION Summary of the Invention

In view of the above problems, the present inventors have extensivelystudied for many years and have found that Rosa roxburghii, Artemisiaeargyi folium and Brassica oleracea var. capitata L. are useful forovercoming the problems. The present invention has been accomplished onthe basis of this finding.

Thus, the present invention provides;

(1) a pharmaceutical composition comprising a pharmaceutically effectiveamount of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. and a pharmaceutically acceptable carrier;

(2) a pharmaceutical composition comprising a pharmaceutically effectiveamount of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL.;

(3) a feedstuff for an animal comprising a substance selected from thegroup consisting of Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L.;

(4) a feedstuff for an animal comprising a substance selected from thegroup consisting of Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L. and a basal diet;

(5) a method for feeding a feedstuff comprising a substance selectedfrom the group consisting of Rosa roxburghii, Artemisiae argyi foliumand Brassica oleracea var. capitata L. to an animal; and

(6) a method for feeding a feedstuff comprising a substance selectedfrom the group consisting of Rosa roxburghii, Artemisiae argyi foliumand Brassica oleracea var. capitata L. and a basal diet to an animal.

In view of the above problems with respect to the use of antibiotics,the present inventors have extensively studied for many years onprotective agents which are safe for animals and have found that Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. have an immunopotentiating activity. The present invention has beenaccomplished on the basis of this finding.

Thus, the present invention provides;

(7) a method for immunopotentiating and protecting from infectiousdiseases, which comprises administering a pharmacologically effectiveamount of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. to an animal;

(8) a use of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. for preparing a medicine for an animal for immunopotentiating andprotecting from infectious diseases;

(9) a use of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. for immunopotentiating and protecting from infectious diseases in ananimal;

(10) a pharmaceutical composition for immunopotentiating and protectingfrom infectious diseases in an animal, comprising a pharmaceuticallyeffective amount of a substance selected from the group consisting ofRosa roxburghii, Artemisiae argyi folium and Brassica oleracea var.capitata L. and a pharmaceutically acceptable carrier;

(11) a medicinal agent for immunopotentiating and protecting frominfectious diseases of an animal, comprising a substance selected fromthe group consisting of Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L. and a pharmaceutically acceptablecarrier; and

(12) a feedstuff for an animal, which is useful for immunopotentiatingand protecting from infectious diseases in an animal, comprising asubstance selected from the group consisting of Rosa roxburghii,Artemisiae argyi folium and Brassica oleracea var. capitata L.

In view of the above problem, the present inventors have extensivelystudied for many years regulating agents for the digestive tract whichare safe for human beings and animals, and have found that Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. have the activity of regulating gastrointestinal functions. Thepresent invention has been accomplished on the basis of this finding.

Thus, the present invention provides;

(13) a method for regulating the digestive tract, which comprisesadministering a pharmacologically effective amount of a substanceselected from the group consisting of Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. to an animal;

(14) a use of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. for preparing a medicine for an animal for regulating the digestivetract;

(15) a use of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. for regulating the digestive tract of an animal;

(16) a pharmaceutical composition for regulating the digestive tract ofan animal, comprising a pharmaceutically effective amount of a substanceselected from the group consisting of Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. and a pharmaceuticallyacceptable carrier;

(17) a medicinal agent for regulating the digestive tract of an animal,comprising a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. and a pharmaceutically acceptable carrier; and

(18) a feedstuff for an animal, which is useful for regulating thedigestive tract of the animal, comprising a substance selected from thegroup consisting of Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L.

To provide an absorbefacient which enables a reduction in the dose of anantibiotic when administered together with the antibiotic, the presentinventors have extensively studied to find out that the absorption of anantibiotic can surprisingly be improved when Rosa roxburghii alone ortwo or more members selected from among Rosa roxburghii, Artemisiaeargyi folium and Brassica oleracea var. capitata L. are administeredsimultaneously with the antibiotic or before or after the administrationof the antibiotic.

Thus, the present invention provides;

(19) a method for improving antibiotic absorption, which comprisesadministering a pharmacologically effective amount of a substanceselected from the group consisting of Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. to an animal;

(20) a use of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. for preparing a medicine for an animal for improving its antibioticabsorption;

(21) a use of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. for improving antibiotic absorption in an animal;

(22) a pharmaceutical composition for improving antibiotic absorption inan animal, comprising a pharmaceutically effective amount of a substanceselected from the group consisting of Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. and a pharmaceuticallyacceptable carrier;

(23) a medicinal agent for improving antibiotic absorption in an animal,comprising a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. and a pharmaceutically acceptable carrier; and

(24) a feedstuff for an animal, which is useful for improving antibioticabsorption in the animal, comprising a substance selected from the groupconsisting of Rosa roxburghii, Artemisiae argyi folium and Brassicaoleracea var. capitata L.

To provide a feedstuff free from the abovementioned defects of anordinary feedstuff and a method of administering the feedstuff toanimals, the present inventors have extensively studied. As a result,they have found that the growth of animals, including fetuses, issurprisingly accelerated by administering Rosa roxburghii alone or twoor more members selected from among Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. to them. The inventorshave further found that an improvement in the egg production rate, eggweight, egg quality or eggshell strength of birds and fishes is alsoaccelerated by them.

Thus, the present invention provides;

(25) a method for accelerating growth of an animal, which comprisesadministering a pharmacologically effective amount of a substanceselected from the group consisting of Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. to the animal;

(26) a use of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. for preparing a medicine for an animal for accelerating growth of theanimal;

(27) a use of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. for accelerating growth of an animal;

(28) a pharmaceutical composition for accelerating the growth of ananimal, comprising a pharmaceutically effective amount of a substanceselected from the group consisting of Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. and a pharmaceuticallyacceptable carrier;

(29) a medicinal agent for accelerating the growth of an animal,comprising a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. and a pharmaceutically acceptable carrier;

(30) a feedstuff for an animal, which is useful for accelerating thegrowth of the animal, comprising a substance selected from the groupconsisting of Rosa roxburghii, Artemisiae argyi folium and Brassicaoleracea var. capitata L.;

(31) a method for improving an egg production rate, egg weight, eggquality or eggshell strength of an animal, which comprises administeringa pharmacologically effective amount of a substance selected from thegroup consisting of Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L. to the animal;

(32) a use of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. for preparing a medicine of an animal for improving an egg productionrate, egg weight, egg quality or eggshell strength of the animal;

(33) a use of a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. for improving an egg production rate, egg weight, egg quality oreggshell strength of an animal;

(34) a pharmaceutical composition for improving an egg production rate,egg weight, egg quality or eggshell strength of an animal, comprising apharmaceutically effective amount of a substance selected from the groupconsisting of Rosa roxburghii, Artemisiae argyi folium and Brassicaoleracea var. capitata L. and a pharmaceutically acceptable carrier;

(35) a medicinal agent for improving an egg production rate, egg weight,egg quality or eggshell strength of an animal, comprising a substanceselected from the group consisting of Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. and a pharmaceuticallyacceptable carrier; and

(36) a feedstuff for an animal, which is useful for improving an eggproduction rate, egg weight, egg quality or eggshell strength of theanimal, comprising a substance selected from the group consisting ofRosa roxburghii, Artemisiae argyi folium and Brassica oleracea var.capitata L.

Further scope and applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

DETAILED DESCRIPTION OF THE INVENTION

Rosa roxburghii is a perennial shrub of the family Rosaceae and isnative to Guizhou in China and its fruit has been noticed as thematerial of juice, jam or liquor. The fruit of Ross roxburghii has beenknown to have a pharmacological activity and is useful as an antiulceragent by virtue of its cancer-preventing, cholesterol level-lowering andantistress activities.

Artemisiae argyi folium is a plant of the family Compositae and has beenknown to be useful as an antidiarrheal or antiabdominalgia agent, ahemostatic or the like. Further, this plant has been known to exhibit alow antimicrobial activity only against Gram-positive bacteria.Artemisiae argyi folium includes, for example, Artemisia princepsPampanini, Artemisia mongolia Fischer, Artemisia argyi LEVL. et VANT.,and Artemisia lavandulaefolia DC.

Brassica oleracea var. capitata L. is a plant of the family Cruciferaeand has been used as food.

The Rosa roxburghii to be used in the present invention is notparticularly limited in form, but may have any form so far as itcontains the essences of Rosa roxburghii. Generally, the fruit of Rosaroxburghii may be used in its raw state or as a dry powder prepared byconventional means prior to use, or an extract prepared by using water,an organic solvent or a mixture of both as an extractant.

The Artemisiae argyi folium and Brassica oleracea var. capitata L. to beused in the present invention are not particularly limited in form, butmay have any form so far as it contains the essences thereof. Generally,the leaf of Artemisiae argyi folium or Brassica oleracea var. capitataL. may be used in a raw state or as a dry powder prepared byconventional means prior to use, or an extract prepared by using water,an organic solvent or a mixture of both as an extractant.

An extract from the above leaves can be prepared by, e.g., a processwhich comprises immersing 1 part by weight of the raw material in 5parts by weight of water, boiling the obtained mixture under heating for30 minutes to conduct extraction, filtering the resulting system, andconcentrating the obtained filtrate to 3.6 parts by weight. The obtainedextract may be powdered by spray drying, freeze drying, vacuum drying(vacuum concentration) of the like.

When an organic solvent is used for extraction, methanol, ethanol,n-propanol, n-butanol, acetone, ethyl acetate, ether, methylenechloride, chloroform, benzene, carbon tetrachloride and petroleum etherare preferable. These organic solvents may be used alone or as a mixtureof two or more of them.

The extracts thus produced may be used as such or may be concentrated,diluted or freed from the solvent prior to use.

The extract of Rosa roxburghii to be used in the present invention maybe one commercially available under the trade name of "Rosa roxburghiiextract powder MF", which is a product of Maruzen Seiyaku K.K.comprising 30% of an extract of Rosa roxburghii and 70% of dextrin.

In the present invention, at least one of Rosa roxburghii, Artemisiaeargyi folium and Brassica oleracea var. capitata L. is(are) used.

When Rosa roxburghii and Artemisiae argyi folium are used in the presentinvention, the ratio between them is not particularly limited.Generally, Artemisiae argyi folium is used, in terms of raw leaf, thatis, when it is prescribed as the weight of raw leaf, in an amount of0.25 to 400 parts by weight, preferably 0.5 to 200 parts by weight,still preferably 1 to 100 parts by weight, based on 1 part by weight ofthe extract of Rosa roxburghii.

When both Artemisiae argyi folium and Brassica oleracea var. capitata L.are used together with Rosa roxburghii, the amounts thereof are notparticularly limited. Generally, Artemisiae argyi folium and Brassicaoleracea var. capitata L. are used in amounts of 0.25 to 400 parts byweight and 0.5 to 800 parts by weight, respectively, in terms of theirrespective raw leaf, based on 1 part by weight of the extract of Rosaroxburghii. It is preferable that Artemisiae argyi folium and Brassicaoleracea var. capitata L. be used in amounts of 0.5 to 200 parts byweight and 1 to 400 parts by weight respectively, still preferably inamounts of 1 to 100 parts by weight and 5 to 200 parts by weightrespectively.

The pharmaceutical composition or the medicinal agent of the presentinvention may be administered, with the purpose of the prevention ofdiseases, as a food having a regulating effect on a living body, i.e., aso-called functional food, which can be prepared by adding thiscomposition or agent to food.

When the pharmaceutical composition or the medicinal agent of thepresent invention comprising one or more members selected from amongRosa roxburghii, Artemisiae argyi folium and Brassica oleracea var.capitata L. is used as a medicine or so-called health food, it may be inthe form of tablet, granule, powder, capsule or syrup. Thepharmaceutical composition or the medicinal agent is prepared by mixingthe members with a conventional filler or carrier, binder, lubricant orthe like and treating the obtained mixture in the conventional manner.

When the pharmaceutical composition or the medicinal agent of thepresent invention comprising one or more members selected from amongRosa roxburghii, Artemisiae argyi folium and Brassica oleracea var.capitata L. is used for an animal, such as a mammal, a bird and a fish,especially for a livestock, the dosage form thereof is not particularlylimited. For example, it may be administered to livestock in a statemixed with a basal diet (or feed or feedstuff). That is, thiscomposition or agent may be mixed with a basal diet (or feed orfeedstuff) just before using or may be premixed with a basal diet (orfeed or feedstuff). In other words, the feedstuff for an animalcomprising a substance selected from the group consisting of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. of the present invention may be administered to an animal as a feedhaving a biophylactic and regulating function.

The arbitrary basal diet for animals, which is used for preparing thefeed stuff according to the present invention, is not particularlylimited. Examples of the raw materials constituting the basal dietinclude grains such as corn, milo and wheat flour, brans such asdefatted rice bran and wheat bran, animal substances such as fish mealand skimmilk. vegetable oil cake such as soybean oil cake, and additivessuch as calcium carbonate, calcium phosphate, common salt, vitamin B₂,DL-methionine, choline chloride, manganese sulfate, dry iron sulfate,calcium iodate, copper sulfate, dry zinc sulfate and sodium saccharin.The basal diet can be prepared by blending some members selected fromamong these materials. The formulation of the basal diet variesdepending upon the animal to which the diet is administered.

The improved feed of the present invention, i.e., the feedstuffcontaining at least one of Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L. can be administered to variouslivestock, poultries, pets and fish. The livestock includes pig, cattle,horse, goat, sheep and rabbit; the poultry chicken, Japanese quail,turkey and duck; the pets dog and cat; and the fish yellowtail, seabream, flatfish, globefish, hardtail, amberjack, salmon, carp, eel,sweetfish, trout, char and lobster.

Needless to say, the pharmaceutical composition, the medicinal agent andthe feedstuff of the present invention are non-toxic.

It will next be described when the pharmaceutical composition, themedicinal agent or the feedstuff of the present invention is used forimmunopotentiating and protecting from infectious diseases.

In this case, Rosa roxburghii, Artemisiae argyi folium and Brassicaoleracea var. capitata L. may be used alone or as a combination of twoor more of them. In other words, the combination of Rosa roxburghii withArtemisiae argyi folium, that of Rosa roxburghii with Brassica olexaceavar. capitata L., that of Artemisiae argyi folium with Brassica oleraceavar. capitata L., and that of Rosa roxburghii with Artemisiae argyifolium and Brassica oleracea var. capitata L. can be used.

Rosa roxburghii, Artemisiae argyi folium and Brassica oleracea var.capitata L. exhibit an immunopotentiating and protective activity evenwhen used each alone. However, the use of a combination of two or moreof them surprisingly exhibits an immunopotentiating and protectiveactivity which is higher than that of the use of each of them.

The pharmaceutical composition or the medicinal agent of the presentinvention can safely and effectively potentiate the immune function oflivestock such as cattle, pig or horse, a poultry such as chicken orJapanese quail, fish such as young yellowtail, sea bream, eel, trout,carp or goldfish, a pet such as dog or cat, or a human being to protectthe animal or the like from various infectious diseases, which is one ofmain objects of the present invention.

The term "immunopotentiation" used in this specification means"potentiation of the immune function of an animal such as a human being,a mammal, fish or the like".

The pharmaceutical composition or the medicinal agent of the presentinvention have the effect of enhancing the immune function of an animal,including a human being, and serves as a preventive and therapeuticpharmaceutical composition or agent for various maladies and infectiousdiseases by virtue of this effect, so that the diseases against whichthis composition or agent is efficacious are not particularly limited.For example, it is efficacious against, e.g., articular rheumatism,autoimmune diseases, bronchial asthma, nutritional disorders, surgicaloperation, diseases of old age and various infectious diseases such asrespiratory infection, sepsis and urinary infection with respect to ahuman being.

With respect to animals other than humans, this composition or agent isefficacious against scours, epizootic pneumonia, atrophic rhinitis andinfectious enterogastritis of a pig, pneumonia and Marek's disease ofchicken, scours, pneumonia and mastitis of cattle, and AIDS and leukemiaof a pet.

Further, with respect to fish, the infectious disease against which thecomposition or agent of the present invention is efficacious is notparticularly limited and includes bacterial diseases such asstreptococcosis and nodosity, and viral diseases.

In this case, the dose of Rosa roxburghii to be administered variesdepending upon the dosage form and the subject animal, so that it is notparticularly limited.

For example, an extract of Rosa roxburghii is administered to livestocksuch as a pig in a dose of 25 mg or above, preferably 50 mg or above,still preferably 100 mg or above per kilogram of the body weight.

It will next be described when the pharmaceutical composition, themedicinal agent or the feedstuff of the present invention is used forregulating the digestive tract.

In this case, Rosa roxburghii is preferably used as the essentialcomponent. The activity of regulating the digestive tract, i.e., thegastrointestinal activity, of the pharmaceutical composition or themedicinal agent is synergistically enhanced when the composition oragent further contains Artemisiae argyi folium or Artemisiae argyifolium and Brassica oleracea var. capitata L. The pharmaceuticalcomposition or the medicinal agent is also used as a component of afeedsuff, and the feedstuff containing the pharmaceutical composition orthe medicinal agent also exhibit the above-described gastrointestinalfunction regulating activity.

The pharmaceutical composition or the medicinal agent of the presentinvention can efficaciously and safely regulate the function(s) of thedigestive tract of livestock such as cattle, pig or horse, poultry suchas chicken or Japanese quail, fish such as young yellowtail, sea bream,eel, trout, carp or goldfish, a pet such as a dog or cat, or humans,which is one of the main objects of the present invention.

The term "digestive tract" to be used in this specification refers tothe organs ranging from the mouth to the anus, particularly to thestomach, duodenum, small intestine, large intestine and rectum.

The term "function(s) of the digestive tract" or "gastrointestinalfunction(s)" used in this specification means digestion, absorption anddigestive motion such as peristalsis. The pharmaceutical composition orthe medicinal agent for the digestive tract according to the presentinvention is useful as a therapeutic and preventive pharmaceuticalcomposition or agent for diarrhea when it acts on the lower part of thedigestive tract, such as the large intestine or rectum, while it isefficacious in alleviating a sharp pain and in moderating gasticemptying and borborygmus when it acts on the upper part thereof, such asthe stomach or duodenum.

When the pharmaceutical composition or the medicinal agent forregulating the function(s) of the digestive tract is used as atherapeutic and preventive pharmaceutical composition or agent fordiarrhea, it is efficacious against various diarrheas which are notlimited in cause and examples of the diarrhea include bacterial diarrheasuch as salmonellosis, viral diarrhea such as caused by adenovirus,parasitic diarrhea such as amebic dysentery, toxic diarrhea such as foodand drug poisoning, allergic diarrhea caused by, e.g., food allergy,functional diarrheas such as cold diarrhea and neurotic diarrhea,diarrheas caused by the use of an antibiotic (such as one caused bymicrobial substitution and staphylococcal diarrhea), and chronicdiarrheas caused by the disorder of digestion and absorption, excess guthormone and colic diseases.

With respect to chickens and pigs, the pharmaceutical composition, themedicinal agent or the feedstuff of the present invention is efficaciousagainst bacterial diarrhea such as caused by Escherichia coli or swinedysentery, vital diarrhea caused by TGE or rotavirus, or simple diarrheasuch as one caused by stress or dietetic diarrhea. Further, it isefficacious also against various diarrheas of fish.

In this case, the dose of Rosa roxburghii to be administered variesdepending upon the dosage form and the subject animal, so that it is notparticularly limited.

For example, an extract of Rosa roxburghii is administered to livestocksuch as a pig in a dose of 20 mg or above, preferably 40 mg or above,still preferably 100 mg or above per kilogram of the body weight.

It will be described about the case that the pharmaceutical composition,the medicinal agent or the feedstuff of the present invention is usedfor improving antibiotic absorption.

In this case, the pharmaceutical composition or the medicinal agentcomprising Rosa roxburghii or a combination of two or more membersselected from among Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L. is administered simultaneously withan antibiotic or before or after the administration of an antibiotic. Asthe pharmaceutical composition or the medicinal agent, Rosa roxburghii,Artemisiae argyi folium and Brassica oleracea var. capitata L. may beeach administered by itself in a raw, dried or pulverized state, or aformulation may be administered. Alternatively, the pharmaceuticalcomposition or the medicinal agent may be added to food or feed in aconventional manner. Namely, the feedstuff comprising a basal diet andat least one of Rosa roxburghii, Artemisiae argyi folium and Brassicaoleracea var. capitata L. of the present invention may be used.

The feedstuff of the present invention is prepared by adding Rosaroxburghii or a combination of two or more members selected from amongRosa roxburghii, Artemisiae argyi folium and Brassica oleracea var.capitata L. to the basal diet described above. The amount of Rosaroxburghii, or the combination, is preferably 0.001% by weight or above,still preferably 0.01% by weight or above in terms of the dried extractthereof, i.e., as the weight of the dried extract thereof.

The pharmaceutical composition, the medicinal agent or the feedstuff forimproving antibiotic absorption according to the present invention maybe administered simultaneously with an antibiotic or, before or afterthe administration of an antibiotic. In any case, the effect ofimproving the absorption of an antibiotic can be attained.

In this case, the dose of Rosa roxburghii or a combination of two ormore members selected from among Rosa roxburghii Artemisiae argyi foliumand Brassica oleracea var. capitata L. is not particularly limited butvaries depending upon the dosage form, the subject animal or the dose ofthe antibiotic.

For example, when the pharmaceutical composition or the medicinal agentfor improving antibiotic absorption comprising two or more membersselected from among Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L. is administered to livestock such asa pig as a powdered extract, the powdered extract is administered in anamount of 0.1 part by weight or above, preferably 1 part by weight orabove, still preferably 3 parts by weight or above based on 1 part byweight of the antibiotic administered. When Rosa roxburghii isadministered alone, the amount thereof may be the same as that describedabove.

It will next be described when the pharmaceutical composition, themedicinal agent or the feedstuff of the present invention is used foraccelerating growth of an animal or improving an egg production rate,egg weight, egg quality or eggshell strength.

One of the objects of the present invention is to provide a novelpharmaceutical composition, medicinal agent or feedstuff foraccelerating growth of an animal, a novel pharmaceutical composition,medicinal agent or feedstuff for improving the egg production rate, eggweight, egg quality or eggshell strength of animals, and a method foradministering them to animals.

More specifically, one of the objects of the present invention is toprovide a novel pharmaceutical composition, medicinal agent or feedstuffwhich can accelerate an increase in the body weight and can improve thesurvival rate, feed conversion ratio of animals, and a novelpharmaceutical composition, medicinal agent or feedstuff which canimprove the survival rate, egg production rate, egg weight, egg quality,eggshell strength and feed conversion ratio of animals.

The term "growth acceleration" or "accelerating growth of an animal" asused herein includes also growth improvement and growth acceleration offetuses. The expression "improvement in the egg production ratio, eggweight, egg quality and eggshell strength" means an improvement in theegg production ratio, an increase in the egg weight, and improvements inthe eggshell and egg quality.

In this case, Rosa roxburghii alone or a combination of two or moremembers selected from among Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L., preferably a combination of threemembers described above, as the active ingredient is administered toanimals. Rosa roxburghii, Artemisiae argyi folium and Brassica oleraceavar. capitata L. can be administered directly to animals or they can beincorporated in the feedstuff or feed by an ordinary method. Namely, thefeedstuff comprising a basal diet and at least one of Rosa roxburghii,Artemisiae argyi folium and Brassica oleracea var. capitata L. of thepresent invention may be used.

The feedstuff of the present invention is prepared by adding Rosaroxburghii alone or a combination of two or more members selected fromamong Rosa roxburghii, Artemisiae argyi folium and Brassica oleraceavar. capitata L. to the basal diet described above. The amount of Rosaroxburghii or the combination is preferably 0.001% by weight or above,still preferably 0.01% by weight or above in terms of the dried extractthereof, i.e., as the weight of the dried extract thereof.

The pharmaceutical composition, the medicinal agent or the feedstuffaccelerates the growth of animals, and improves the rate of raising orfeed conversion rate. When it is administered to birds and fishes, itaccelerates an improvement in the egg production rate, egg weight, eggquality or eggshell strength of them.

The dose of Rosa roxburghii is not particularly limited in this case,since it varies depending on the dosage form thereof and the subjectanimal.

When Rosa roxburghii extract is administered to livestock, such ascattle and pigs, the amount thereof is usually at least 10 mg,preferably at least 50 mg and still preferably at least 100 mg, based on1 kilogram of the body weight thereof.

EXAMPLES

The present invention will now be described in more detail withreference to the following Examples which should not be considered tolimit the scope of the present invention.

In the Examples, the description of the dose of each component, e.g.,"10 mg/kg p.o." means oral administration in a dose of 10 mg perkilogram of body weight. Further, the symbols "*" and "**" used in thecolumn of the x² test in Tables mean p<0.05 and p<0.01, respectively.

The Rosa roxburghii used in Examples A-1, B-1 and B-2 is onecommercially available under the trade name of "Rosa roxburghii extractpowder MF", which is a product of Maruzen Seiyaku K K comprising 30% ofan extract of Rosa roxburghii and 70% dextrin. The dose of Rosaroxburghii is expressed in terms of the weight of this extract powder.The dose of Actemisiae argyi folium is expressed in terms of the weightof an extract thereof having 4-fold concentration with respect to itsnormal weight, while the dose of Brassica oleracea var. capitata L. isexpressed in terms of the weight of an extract having a 9-foldconcentration with respect to its normal weight.

Example A-1

As shown in Tables A-1 and A-2, Rosa roxburhii, Artemisiae argyi foliumand Brassica oleracea var. capitata L. were each orally administeredalone (Table A-1), or as a mixture of two or more of them (Table A-2),to ten SLC:ICR male mice (age: 5 to 6 weeks, weight: 25 to 33 g) indoses of 500 to 2000 mg/kg, while physiological saline was orallyadministered thereto as a control. After 24 hours, clinically availableEscherichia coli (5.0×10⁷ CFU/mouse, 0.2 ml) was intravenouslyinoculated into each mouse to determine the survival rate based on thenumber of viable mice after 7 days from the infection. The results aregiven in Tables A-1 and A-2.

                  TABLE A-1    ______________________________________                                      x.sup.2    Sample               Survival rate (%)                                      test    ______________________________________    control (physiological saline p.o.)                         0    Artemisiae argyi folium 500 mg/Kg p.o.                         20    Artemisiae argyi folium 1000 mg/Kg p.o.                         30    Artemisiae argyi folium 2000 mg/Kg p.o.                         50           *    Brassica oleracea var. capitata L.                         10    500 mg/Kg p.o.    Brassica oleracea var. capitata L.                         30    1000 mg/Kg p.o.    Brassica oleracea var. capitata L.                         40           *    2000 mg/Kg p.p.    Rosa roxburghii 500 mg/Kg p.o.                         20    Rosa roxburghii 1000 mg/Kg p.o.                         30    Rosa roxburghii 2000 mg/Kg p.o.                         50           *    ______________________________________

                  TABLE A-2    ______________________________________                             Survival x.sup.2    Sample                   rate (%) test    ______________________________________    control (physiological saline p.o.)                             0    Artemisiae argyi folium 500 mg/Kg p.o. and                             40       *    Brassica oleracea var. capitata L. 500 mg/Kg p.o.    Artemisiae argyi folium 1000 mg/Kg p.o. and                             70       *    Brassica oleracea var. capitata L.    1000 mg/Kg p.o.    Artemisiae argyi folium 2000 mg/Kg p.o. and                             100      **    Brassica oleracea var. capitata L.    2000 mg/Kg p.o.    Rosa roxburghii 500 mg/Kg p.o. and                             60       *    Artemisiae argyi folium 500 mg/Kg p.o.    Rosa roxburghii 1000 mg/Kg p.o. and                             90       **    Artemisiae argyi folium 1000 mg/Kg p.o.    Rosa roxburghii 2000 mg/Kg p.o. and                             100      **    Artemisiae argyi folium 2000 mg/Kg p.o.    Rosa roxburghii 500 mg/Kg p.o.,                             70       *    Artemisiae argyi folium 500 mg/Kg p.o. and    Brassica oleracea var. capitata L. 500 mg/Kg p.o.    Rosa roxburghii 1000 mg/Kg p.o.,                             100      **    Artemisiae argyi folium 1000 mg/Kg p.o. and    Brassica oleracea var. capitata L.    1000 mg/Kg p.o.    ______________________________________

As shown in Table A-1, the survival rate increases depending upon thedose of Rosa roxburghii, Artemisiae argyi folium or Brassica oleraceavar. capitata L., which reveals that these plants have a protectiveeffect.

As shown in Table A-2, the simultaneous use of Rosa roxburghii withArtemisiae argyi folium, that of Artemisiae argyi folium with Brassicaoleracea var. capitata L. and that of Rosa roxburghii with Artemisiaeargyi folium and Brassica oleracea var. capitata L. exhibit theprotective effect exceeding the arithmetic sum of the respective effectsof these plants. That is, the above simultaneous use exhibits asignificant synergistic effect, being of great value.

The above test in Example A-1 reveals that the medicinal agent forimmunopotentiating and protecting from infectious diseases of thepresent invention has an excellent protective activity againstGram-negative bacteria, which suggests that the agent of the presentinvention is not one which exhibits a low antimicrobial activity onlyagainst Gram-positive bacteria like Escherichia coli, but one whichpotentiates the immune function itself. Accordingly, the agent of thepresent invention is effective in the prevention and treatment ofvarious maladies and useful as a preventive and therapeutic agent forvarious infectious diseases or as a functional food or feed. Thus, thepresent invention is of great value.

Example B-1

As shown in Table B-1, Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L. were each orally administered to sixSLC:SD male rats (age: 6 weeks, weight: 250 to 300 g) in a dose of 125to 500 mg/kg, while physiological saline was orally administered theretoas a control. After 30 minutes, 1 ml of caster oil was further orallyadministered to the rats to determine the time which elapsed until theoccurrence of diarrhea and the total amount of excrement given within 2hours of the administration. The antidiarrheal index of each case wascalculated from these values according to the following formula 1 toevaluate the antidiarrheal activity. The measured values and theantidiarrheal index are given in Table B-1. ##EQU1##

                  TABLE B-1    ______________________________________                   Time until                   the       Total                   occurrence                             amount of  Anti-                   of diarrhea                             excrement  diarrheal    Sample         (min)     (g)        index    ______________________________________    control (physiological                   38.5 ± 5.9                             6.7 ± 0.67                                        1.00    saline p.o.)    Artemisiae argyi                   53.3 ± 13.8                             4.5 ± 0.83                                        2.06    folium 125 mg/Kg p.o.    Artemisiae argyi                   71.8 ± 18.4                             3.7 ± 1.09                                        3.38    folium 250 mg/Kg p.o.    Artemisiae argyi                   95.8 ± 12.8                             2.0 ± 0.68                                        8.33    folium 500 mg/Kg p.o.    Brassica oleracea var.                   45.3 ± 7.9                             5.9 ± 1.16                                        1.36    capitata L. 125 mg/Kg p.o.    Brassica oleracea var.                   49.5 ± 10.7                             4.7 ± 1.14                                        1.83    capitata L. 250 mg/Kg p.o.    Brassica oleracea var.                   51.2 ± 8.2                             3.8 ± 1.21                                        2.34    capitata L. 500 mg/Kg p.o.    Rosa roxburghii                   50.5 ± 10.0                             4.2 ± 1.67                                        2.09    125 mg/Kg p.o.    Rosa roxburghii                   68.3 ± 6.4                             3.7 ± 0.80                                        3.21    250 mg/Kg p.o.    Rosa roxburghii                   77.8 ± 14.4                             1.8 ± 0.70                                        7.52    500 mg/Kg p.o.    ______________________________________

It was ascertained from the results given in

Table B-1 that Artemisiae argyi folium, Rosa roxburghii and Brassicaoleracea var. capitata L. had an antidiarrheal activity.

Example B-2

As shown in Tables B-2 and B-3, two or more members selected from amongRosa roxburghii, Artemisiae argyi folium and Brassica oleracea var.capitata L. were orally administered to six SLC:SD male rats (age: 6weeks, weight: 250 to 300 g) each in doses of 125 to 500 mg/kg, whilephysiological saline was orally administered thereto as a control. After30 minutes, 1 ml of castor oil was further administered orally to therats to determine the time elapsed until the occurrence of diarrhea andthe total amount of the excrement given within 2 hours of theadministration. The antidiarrheal index of each case was calculated fromthese values according to the above formula 1 to evaluate theantidiarrheal activity. The measured values and the antidiarrheal indexare given in Tables B-2 and B-3.

                  TABLE B-2    ______________________________________                   Time until                   the        Total                   occurrence amount of Anti-                   of diarrhea                              excrement diarrheal    Sample         (min)      (g)       index    ______________________________________    control (physiological                   38.5 ± 5.9                              6.7 ± 0.67                                        1.00    saline p.o.)    Artemisiae argyi folium 125                   62.7 ± 13.4                              4.2 ± 1.02                                        2.60    mg/Kg p.o. and Brassica    oleracea var. capitata L.    125 mg/Kg p.o.    Artemisiae argyi folium 250                   83.5 ± 15.3                              3.2 ± 1.45                                        4.54    mg/Kg p.o. and Brassica    oleracea var. capitata L.    250 mg/Kg p.o.    Artemisiae argyi folium 500                   99.3 ± 13.2                              1.8 ± 0.70                                        9.59    mg/Kg p.o. and Brassica    oleracea var. capitata L.    500 mg/Kg p.o.    Rosa roxburghii                   78.4 ± 8.6                              3.5 ± 1.73                                        3.89    125 mg/Kg p.o. and    Artemisiae argyi folium    125 mg/Kg p.o.    Rosa roxburghii                   90.3 ± 12.4                              2.6 ± 1.17                                        6.04    250 mg/Kg p.o. and    Artemisiae argyi folium    250 mg/Kg p.o.    Rosa roxburghii    500 mg/Kg p.o. and                   101.8 ± 14.3                              1.6 ± 1.58                                        11.06    Artemisiae argyi folium    500 mg/Kg p.o.    ______________________________________

                  TABLE B-3    ______________________________________                   Time until                   the        Total                   occurrence amount of Anti-                   of diarrhea                              excrement diarrheal    Sample         (min)      (g)       index    ______________________________________    control (physiological                   38.5 ± 5.9                              6.7 ± 0.67                                        1.00    saline p.o.)    Rosa roxburghii 125                    91.5 ± 17.4                              3.5 ± 1.73                                        6.37    mg/Kg p.o., Artemisiae    argyi folium 125 mg/Kg    p.o. and Brassica    oleracea var. capitata L.    125 mg/Kg p.o.    Rosa roxburghii 250                   102.0 ± 13.0                              1.8 ± 0.70                                        9.85    mg/Kg p.o., Artemisiae    argyi folium 250 mg/Kg    p.o. and Brassica    oleracea var. capitata L.    250 mg/Kg p.o.    Rosa roxburghii 500    mg/Kg p.o., Artemisiae    argyi folium 500 mg/Kg                   110.8 ± 14.0                              1.3 ± 1.16                                        14.82    p.o. and Brassica    oleracea var. capitata L.    500 mg/Kg p.o.    ______________________________________

It has been ascertained from the results given in Tables B-1 and B-2that the simultaneous use of Rosa roxburghii with Artemisiae argyifolium exhibits a synergistic antidiarrheal activity, while it has beenascertained from the results given in Tables B-1 and B-3 that thesimultaneous use of Rosa roxburghii with Artemisiae argyi folium andBrassica oleracea var. capitata L. also exhibits a synergisticantidiarrheal activity.

The above test in Examples B-1 and B-2 reveals that the medicinal agentfor regulating a function of a digestive tract according to the presentinvention has an excellent antidiarrheal activity. Accordingly, themedicinal agent for regulating a function of a digestive tract of thepresent invention is effective in the prevention and treatment ofdiarrhea caused by various diseases, and is useful as a preventive ortherapeutic agent for diarrhea or a functional food or feed. Thus, thepresent invention is of great value.

The mixture of Rosa roxburghii, Artemisiae argyi folium and Brassicaoleracea var. capitata L. used in the following Examples C-1, C-2, D-1to D-6 were prepared as follows:

Raw leaves (3 kg) of Artemisiae argyi folium were immersed in 15 l ofwater and the obtained mixture was boiled for 30 minutes to conductextraction. The resulting mixture was filtered to recover a filtrate.The filtrate was concentrated to 1.8 kg by heating to give an extract.This extract was powdered by spray drying to give a dry powder of theextract of Artemisiae argyi folium. Similarly, Brassica oleracea var.capitata L. was also converted into a dry powder of the extract thereof.1500 g of Rosa roxburghii extract powder MF (a product of MaruzenSeiyaku K.K. comprising 30% of an extract of Rosa roxburghii and 70% ofdextrin) was mixed with 675 g of the above dry powder of the extract ofArtemisiae argyi folium and 225 g of the above dry powder of the extractof Brassica oleracea var. capitata L. to give 2400 g of a mixed powder(a weight ratio of Rosa roxburghii:Artemisiae argyi folium:Brassicaoleracea var. capitata L. being 2:3:1).

Example C-1

The above mixture of the dry powders or each of the dry powders wasorally administered to four SLC:ICR male mice (age: 5 to 6 weeks,weight: 25 to 33 g) in a dose given in Table C-1 together with 10 mg perkilogram of the body weight of amoxicillin (hereinafter referred tosimply as "AMPC") as an antibiotic. After 2 hours, blood was gatheredfrom the mice to determine the serum AMPC concentrations, which werecompared with those of mice to which AMPC alone had been administered.Each serum AMPC concentration was determined by using a strain ofSarcina luteas (Gram-positive and AMPC-sensitive bacterium) according tothe disk method (this method of measurement was also employed in ExampleC-2).

The results are given in Table C-1.

                  TABLE C-1    ______________________________________                    Serum AMPC concn. μg/ml                    (figures in parentheses                    being ratio thereof to                    the concn. of control)    ______________________________________    AMPC 10 mg/kg (control)                      2.12 ± 1.14 (1.00)    AMPC 10 mg/kg + a mixed                      2.70 ± 1.22 (1.27)    powder of Rosa roxburghii,    Artemisiae argyi folium    and Brassica oleracea var.    capitata L. 10 mg/kg    AMPC 10 mg/kg + a mixed                      3.04 ± 1.22 (1.43)    powder of Rosa roxburghii,    Artemisiae argyi folium    and Brassica oleracea var.    capitata L. 30 mg/kg    AMPC 10 mg/kg + a mixed                      3.11 ± 1.97 (1.47)    powder of Rosa roxburghii,    Artemisiae argyi folium    and Brassica oleracea var.    capitata L. 90 mg/kg    AMPC 10 mg/kg + a mixed                      3.53 ± 1.93 (1.67)*    powder of Rosa roxburghii,    Artemisiae argyi folium    and Brassica oleracea var.    capitata L. 190 mg/kg    AMPC 10 mg/kg + a mixed                      5.62 ± 0.57 (2.65)**    powder of Rosa roxburghii,    Artemisiae argyi folium    and Brassica oleracea var.    capitata L. 2000 mg/kg    AMPC 10 mg/kg + Rosa                      4.87 ± 1.81 (2.30)**    roxburghii 10 mg/kg    AMPC 10 mg/kg + Artemisiae                      2.95 ± 1.13 (1.39)    argyi folium 10 mg/kg    AMPC 10 mg/kg +Brassica                      2.20 ± 1.11 (1.04)    oleracea var. capitata L.    10 mg/kg    ______________________________________

As shown in Table C-1, the group of the mice to which AMPC and Rosaroxburghii had been administered and the groups of the mice to whichAMPC, Rosa roxburghii, Artemisiae argyi folium and Brassica oleraceavar. capitata L. had been administered were apparently improved in theabsorption of AMPC depending upon the dose thereof as compared with thegroup of the mice to which AMPC alone and been administered.

Example C-2

AMPC (10 mg/kg) alone or the mixture of AMPC (10 mg/kg) with the mixeddry powder (30 mg/kg) comprising Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. was administered to sixSPF male pigs (age: 1 month, weight: about 15 kg) mixed with a basaldiet to gather blood from the pigs after 0.5, 1, 2, 3 and 6 hours. Theserum AMPC concentrations of the pigs to which AMPC and the mixed drypowder had been administered were determined and compared with those ofthe pigs to which AMPC alone had been administered.

The results are given in Table C-2.

The formulation of the above basal diet are given in Table C-3.

                                      TABLE C-2    __________________________________________________________________________                       after after after after after                       0.5 hr                             1 hr  2 hrs 3 hrs 6 hrs    __________________________________________________________________________    AMPC 10 mg/kg (control)                       3.07 ± 1.55                             6.03 ± 0.80                                   3.71 ± 0.63                                         2.10 ± 0.40                                               0.85 ± 0.75    AMPC 10 mg/kg + a mixed powder of                       6.03 ± 1.49                             7.81 ± 1.49                                   5.85 ± 0.80                                         3.71 ± 1.41                                               1.74 ± 1.16    Rosa roxburghii, Artemisiae argyi                       (1.63)**                             (1.30)*                                   (1.58)**                                         (1.77)*                                               (2.05)**    folium and Brassica oleracea var.    capitata L. 30 mg/kg    __________________________________________________________________________     note)     Serum AMPC concentration, μg/ml     The figures in parentheses are the ratios of the serum AMPC concentration     to that of the control.

                  TABLE C-3    ______________________________________                    Initiation of    Administration  feeding to 5                               5 to 7 weeks    period          weeks of age                               of age    Component       Amt. (%)   Amt. (%)    ______________________________________    parched wheat   33.8       20.0    glucose         9.0        5.0    sugar           3.0        --    wheat flour     --         20.0    yellow corn     --         23.6    skimmilk powder 40.0       10.0    fish meal       3.0        5.0    soybean oil cake                    3.0        9.0    Torula yeast    2.0        2.0    soybean oil     4.0        3.0    common salt     0.2        0.2    tricalcium phosphate                    1.2        1.4    mineral mixture 0.2        0.2    vitamin mixture 0.2        0.2    flavor, antibiotic and                    0.4        0.4    other feed additives    ______________________________________

As shown in Table C-2, the pigs to which AMPC and the mixed powder hadbeen administered were apparently improved in the absorption of AMPCover a period of 0.5 to 6 hours after the administration as comparedwith the pigs to which AMPC alone had been administered.

The results of the above tests suggest that the medicinal agent forimproving antibiotic absorption and the feedstuff according to thepresent invention are so efficacious in improving the absorption of anantibiotic that the dose of the antibiotic can be reduced. Accordingly,the present invention is of great value.

Example D-1

40 sound pigs (castrated pigs of about 10 days old; 3.0 to 3.5 kg) weredivided into four groups, i.e., three groups each consisting of ten pigsto which the mixed powder comprising Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. were administered and acontrol group consisting of ten pigs to which an ordinary basal dietfree of Rosa roxburghii, Artemisiae argyi folium and Brassica oleraceavar. capitata L. was administered. A feedstuff enriched with the mixedpowder of Rosa roxburghii, Artemisiae argyi folium and Brassica oleraceavar. capitata L. in amounts of 0.03, 0.1 or 0.3% by weight wasadministered to the pigs of one of the three groups for 30 days. After30 days, the intake of the feedstuff and the gain of body weight weredetermined to calculate the rate of raising and the feed conversionratio (feedstuff intake/gain of body weight). The results were comparedwith those of the control group.

The composition of the artificial milk-based basal diet for piglings wasas shown in Table D-1.

The results of the groups to which Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. were administered and thecontrol group were compared with each other. The t-test was conductedfor the gain of body weight in the control group and the groups of thepresent invention. Table D-2 shows the results.

                  TABLE D-1    ______________________________________                     Initiation of                     feeding to 5                                5 to 7 weeks    Feeding period   weeks of age                                of age    Component        Amt. (%)   Amt. (%)    ______________________________________    Roast wheat      33.8       20.0    Glucose          9.0        5.0    Sugar            3.0        --    Wheat flour      --         20.0    Yellow corn      --         23.6    Skim milk powder 40.0       10.0    Fish meal        3.0        5.0    Soybean oil cake 3.0        9.0    Torula yeast     2.0        2.0    Soybean oil      4.0        3.0    Common salt      0.2        0.2    Tricalcium phosphate                     1.2        1.4    Mineral mixture  0.2        0.2    Vitamin mixture  0.2        0.2    Flavor, antibiotic                     0.4        0.4    and other feed additives    ______________________________________

                  TABLE D-2    ______________________________________            Feedstuff Gain of     Feed            intake    body weight conversion            (A)       (B)         ratio   Rate of    Group   (kg/pig)  (kg/pig)    (A/B)   raising    ______________________________________    Test group            11.24     5.3 ± 1.33**                                  2.12    88.8%    (0.03%)    Test group            11.79     6.3 ± 1.61**                                  1.87    93.0%    (0.1%)    Test group            12.32     5.7 ± 1.04*                                  2.16     100%    (0.3%)    Control 8.50      3.4 ± 1.15                                  2.50    81.9%    group    ______________________________________

The gain of body weight per pig in the groups to which Rosa roxburghii,Artemisiae argyi folium and Brassica oleracea var. capitata L. wereadministered was larger than that in the control group, and the feedconversion ratio and the rate of raising were increased in the formergroup.

Example D-2

18 bull Holstein calves of about 7 days old were divided into threegroups, i.e., two groups each consisting of six calves to which Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. were administered and a control group consisting of six calves towhich neither of Rosa roxburghii, Artemisiae argyi folium and Brassicaoleracea var. capitata L. was administered. The mixed powder of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. was mixed into a milk substitute for raising suckling calves and intoa feedstuff containing a milk substitute (artificial milk) for raisingsuckling calves in an amount of 0.125 or 0.25% by weight based on thebasal diet. The milk substitute or the feedstuff was repeatedlyadministered for 20 days. The dose of the mixed powder was 2.5 g/day or5 g/day per calf. Each calf was weighed at the beginning of the test andafter the completion of the test (after 20 days) to calculate the gainof body weight and the rate of body weight gain per day.

The composition of the feedstuff containing the milk substitute forraising suckling calves was as shown in Table D-3.

The results of the groups to which Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. were administered andthose of the control group are compared with each other. The t-test wasconducted in the control group and the groups of the present invention.

Table D-4 shows the results.

                  TABLE D-3    ______________________________________    Component        Amt. (%)    ______________________________________    Skim milk powder 60.0    Dry whey         14.8    Animal fat or oil                     20.0    Fish soluble     4.0    Vitamin mixture  0.5    Mineral mixture  0.7    ______________________________________

                  TABLE D-4    ______________________________________                 Gain of body                            Gain of body                 weight     weight    Group        (kg/calf)  (kg/calf/day)    ______________________________________    Test group   41.0 ± 7.45**                            2.05 ± 0.29**    2.5 g/day    Test group   42.5 ± 5.69**                            2.13 ± 0.27**    5.0 g/day    Control      25.7 ± 8.32                            1.29 ± 0.36    group    ______________________________________

The gain of body weight per day in the groups to which Rosa roxburghii,Artemisiae argyi folium and Brassica oleracea var. capitata L. wereadministered was larger than that in the control group, and the rate ofbody weight gain was increased in the former group.

Example D-3

80 pullet broilers (chunky) were divided into two groups, i.e., a groupconsisting of 40 broilers to which Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. were administered and acontrol group consisting of 40 broilers to which neither of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. was administered.

The mixed powder of Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L. was administered in an amount of 0.1%by weight based on the basal diet for broilers to the group, to whichRosa roxburghii, Artemisiae argyi folium and Brassica oleracea var.capitata L. were administered, for 6 weeks. Each broiler was weighed atthe beginning of the test and after 6 weeks. The average gain of bodyweight in the group to which Rosa roxburghii, Artemisiae argyi foliumand Brassica oleracea var. capitata L. were administered and that in thecontrol group were calculated.

The composition of the basal diet for broilers was as shown in TableD-5.

The results of the group to which Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. were administered andthose of the control group are compared with each other. The x² -testfor the average gain of body weight was conducted in the control groupand the group to which Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L. were administered.

Table D-6 shows the results.

                  TABLE D-5    ______________________________________                  Initiation                  of feeding 3 to 5    5 to 6                  to 3 weeks weeks of  weeks of    Feeding period                  of age     age       age    Component     Amt. (%)   Amt. (%)  Amt. (%)    ______________________________________    Corn          50.45      55.30     55.34    Milo          10.0       15.0      15.01    Soybean oil cake                  18.0       13.0      13.01    Rapeseed oil cake                  --         2.5       2.51    Fish meal     8.0        5.0       5.01    Fish soluble  2.0        --        --    Absorbent feed                  3.0        --        --    Gluten meal    Alfalfa meal  2.0        --        --    Torula yeast  1.0        --        --    Meat/bone meal                  --         3.0       3.0    Raw rice bran --         2.0       2.0    Animal fat or oil                  3.3        2.8       2.81    Common salt   0.25       0.25      0.25    Calcium carbonate                  0.6        0.3       0.30    Dicalcium phosphate                  0.8        0.5       0.5    Lysine        --         --        --    Methionine    0.18       --        --    Vitamin mixture                  0.1        0.1       0.1    Choline chloride                  0.05       0.06      0.06    Mineral mixture                  0.1        0.1       0.1    Flavor, antibiotic and                  0.17       0.09      --    other feed additives    ______________________________________

                  TABLE D-6    ______________________________________               Av. body wt.               at initiation                          Av. body wt.                                     Av. gain of               of feeding after 6 weeks                                     body weight    Group      (g/broiler)                          (g/broiler)                                     (g/broiler)    ______________________________________    Test group 43.8 ± 0.08                          2065 ± 8.7                                     2021.7 ± 8.6**    (0.1%)    Control group               43.6 ± 0.07                          1879 ± 10.2                                     1835.4 ± 10.1    ______________________________________

The increase in the average body weight in the group to which Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. were administered was larger than that in the control group.

Example D-4

12,000 young yellowtails having an average body weight of about 600 gwere divided into two groups, i.e., a group consisting of 6,000 youngyellowtails to which Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L. were administered and a control groupconsisting of 6,000 young yellowtails to which neither of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. was administered. The mixed powder of Rosa roxburghii, Artemisiaeargyi folium and Brassica oleracea var. capitata L. were mixed with abasal diet for young yellowtails (Moist pellets) in an amount of 0.5% byweight based on the basal diet and the resultant mixture wasadministered to them at intervals of three days for one month. Theresults were compared with those of the control group. The youngyellowtails were raised in a crawl having a size of about 3 m×3 m×3 m.During the test period, the feedstuff was administered once a day in anamount of about 3% by weight based on the body weight a day.

The composition of the basal diet for young yellowtails was as shown inTable D-7.

The death rate during the test period in the group to which Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. were administered and that in the control group were compared witheach other to evaluate the effect of improving the rate of raising. Thex² -test was conducted in the control group and the group of the presentinvention.

The results are given in Table D-8.

                  TABLE D-7    ______________________________________    Component        Amt. (%)    ______________________________________    Fish meal        56.0    Meat/bone meal   3.0    Soybean oil cake 5.0    Corn gluten meal 3.0    Torula yeast     2.0    Wheat flour      28.4    Vitamin mixture  1.0    Choline chloride 0.3    Inorg. mixture   1.0    Sodium polyacrylate                     0.3    ______________________________________

                  TABLE D-8    ______________________________________                     No. of   No. of died                     samples  samples    Group            (fish)   (fish)    ______________________________________    Test group (0.1%)                     6000     180**    control group    6000     750    ______________________________________

The death rate during the test period in the group to which Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. were administered was far smaller than that in the control group toprove the effect of improving the rate of raising.

Example D-5

0.01, 0.03 or 0.10%, based on the amount of the mixed extract powdercomprising Rosa roxburghii, Artemisiae argyi folium and Brassicaoleracea var. capitata L. used in a pellet for mice and rats, of apreparation prepared by spraying an aqueous suspension of the mixedextract powder followed by drying, was used to form the pellet for miceand rats. Each feedstuff containing Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. thus prepared wasadministered to each group of male slc:SD rats, which consisted of 8rats of 21 days old (body weight: 50 to 57 g), for one month and theneach rat was weighed to calculate the rate of body weight gain.

The composition of the basal diet for rats (pellet) was as shown inTable D-9.

The body weights of the rats weighed during the test period in the groupto which Rosa roxburghii, Artemisiae argyi folium and Brassica oleraceavar. capitata L. were administered were compared with those in thecontrol group to examine the effect on the gain of body weight in bothgroups. The t-test was conducted in the control group and the groups towhich Rosa roxburghii, Artemisiae argyi folium and Brassica oleraceavar. capitata L.

The results are given in Table D-10

                  TABLE D-9    ______________________________________    Component        Amt. (%)    ______________________________________    Casein           14.12    Corn starch      58.40    Glucose          12.83    Soybean oil      5.45    Cellulose        5.00    Minerals         4.00    Vitamins A and D 0.10    Vitamin B        0.10    ______________________________________

                  TABLE D-10    ______________________________________    Average body weight (g) and rate    of body weight gain in each group    Group   0 week   1 week   2 weeks                                     3 weeks                                            4 weeks    ______________________________________    Test group            52.9 ±                     106.7 ±                              162.4 ±                                     213.4 ±                                            258.2 ±    (0.03%) 1.48     4.29     7.17   6.95   7.70            (1.00)   (2.02)   (3.06) (4.03) (4.86)*    Test group            53.2 ±                     107.6 ±                              162.6 ±                                     216.3 ±                                            258.5 ±    (0.1%)  1.83     3.77     7.28   9.41   10.96            (1.00)   (2.02)   (3.06) (4.07) (4.88)*    Test group            53.7 ±                     107.6 ±                              166.7 ±                                     221.4 ±                                            270.2 ±    (0.3%)  2.65     3.23     6.09   10.61  12.53            (1.00)   (2.00)   (3.10) (4.12) (5.03)**    Control 53.8 ±                     102.9 ±                              157.3 ±                                     204.5 ±                                            241.9 ±    group   1.38     5.23     9.91   13.41  17.08            (1.00)   (1.91)   (2.92) (3.80) (4.50)    ______________________________________

After the administration of Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L., an increment in the rate of bodyweight gain of 0.23 to 0.53 was recognized depending on the dose, ascompared with the control group.

Example D-6

The tests were conducted twice by using groups of Dekalb-TX chickens of182 days old (average body weight: 1.5 kg). Each group consisted of 8chickens. The average results are given in Table D-11 and D-12. In thetest, the chickens were divided into three groups, i.e., a group towhich 0.03% of the mixed powder of Rosa roxburghii, Artemisiae argyifolium and Brassica oleracea var. capitata L. was administered, a groupto which 0.1% of the mixed powder was administered, and the controlgroup. The feeding was conducted for a period of 18 days.

After the completion of the feeding, body weight and egg weightdetermination, egg quality test and eggshell strength determination(with an eggshell strength meter) were conducted. Further, the feedconversion ratio (feedstuff intake/gain of body weight) was calculated.

The results are given in Tables D-11 and D-12.

                  TABLE D-11    ______________________________________              Egg                    Feed              prodn.    Egg weight/day                                     conversion    Group     rate      (g/chicken · day)                                     ratio    ______________________________________    Test group              79.7%     47.3         2.14    (0.03%)    Test group              79.3%     46.6         2.28    (0.1%)    Control   74.2%     44.2         2.34    group    ______________________________________     Note)     Egg weight/day indicates the total weight of eggs laid by a chicken a day

                  TABLE D-12    ______________________________________              Eggshell     Eggshell              strength     thickness                                    Eggshell    Group     (kg/cm.sup.2)                           (mm)     (wt. %)    ______________________________________    Test group              3.40         0.358    10.6    (0.03%)    Test group              3.16         0.359    10.4    (0.1%)    Control   3.12         0.374    10.5    group    ______________________________________

It will be apparent from Table D-11 that the egg production rate, eggweight and feed conversion ratio were increased more remarkably in thegroup to which Rosa roxburghii, Artemisiae argyi folium and Brassicaoleracea var. capirate L. had been administered than those in thecontrol group.

It will be apparent from Table D-12 that as compared with the thicknessof the eggshell, the eggshell strength was more increased in the groupto which Rosa roxburghii, Artemisiae argyi folium and Brassica oleraceavar. capitata L. had been administered than that in the control group.The results promise the prevention of egg cracking.

One embodiment of the present invention provides a medicinal agent oranimal feedstuff for accelerating growth of an animal which comprisesRosa roxburghii alone or Rosa roxburghii, Artemisiae argyi folium andBrassica oleracea var. capitata L. to be administered to animalsdirectly or as additives to be incorporated into a basal diet so as toimprove the body weight gain, survival rate and feed conversion ratio ofan animal; and another embodiment of the present invention provides amedicinal agent for improving an egg production rate, egg weight, eggquality or eggshell strength of animals. Since Rosa roxburghii,Artemisiae argyi folium and Brassica oleracea var. capitata L. are used,a high degree of safety is afforded and no environmental pollution iscaused. Further, Rosa roxburghii, Artemisiae argyi folium and Brassicaoleracea var. capitata L. are available at low costs and are excellentas a medicinal agent or animal feedstuff for accelerating growth of ananimal and a medicinal agent for improving an egg production rate, eggweight, egg quality or eggshell strength of an animal and have a highstorageability.

The invention being thus described, it will be obvious that the same maybe varied in many ways. Such variations are not to be regarded as adeparture from the spirit and scope of the invention, and all suchmodifications as would be obvious to one skilled in the art are intendedto be included within the scope of the following claims.

What we claim is:
 1. A method for immunopotentiating and protecting ananimal from an infection caused by Escherichia coli, which comprisesadministering a pharmaceutically effective amount of a mixture of Rosaroxburghii, Artemisiae argyi folium and Brassica oleracea var. capitataL. to the animal.
 2. The method of claim 1, wherein said infection isselected from the group consisting of a respiratory infection, sepsisand a urinary infection.
 3. The method for immunopotentiating andprotecting from an infection according to claim 1, wherein the mixtureis an extract thereof.
 4. The method for immunopotentiating andprotecting from an infection according to claim 1, wherein the animal isa mammal.
 5. The method for immunopotentiating and protecting from aninfection according to claim 4, wherein the mammal is a human.